The Institute of Parasitic Diseases of the Chinese Academy of Preventive Medicine has recently completed a four year nationwide survey of parasitic infections among almost 1.5 million individuals in every Province of P.R. China. Striking findings from the study were 1) the apparent emergence of hookworm infection and paragonimiasis superimposed on an alarming prevalence of schistosomiasis japonica, particularly in high population density areas of the Yangtze River Basin and 2) the unsatisfactory effectiveness of traditional control methods that rely on broad spectrum anthelminthics. We propose to employ modern and innovative biotechnology for the study and control of these three major helminthiases in the Yangtze River Basin. Our Institute has assembled teams of parasitologists, molecular biologists and immunologists/vaccinologists to collaborate with U.S. and Australian institutions on two fronts. The first approach proposes to develop molecular vaccines (recombinant polypeptides and DNA vaccines) against all three helminthiases. We are currently testing a promising recombinant anti-disease vaccine candidate against schistosomiasis japonica that was genetically engineered at our Institute, with several other candidates in active development. We are also testing two recombinant anti-disease vaccine candidates for hookworm infection that were genetically engineered at Yale. A major thrust of the proposal will be to research and develop additional vaccine candidates jointly with our foreign collaborators. The second approach will be to determine the extent of genetic diversity among the Chinese strains of these helminths and their vectors. For this, we will build on a well developed collaboration with the Academy of Natural Sciences in Philadelphia through our recently established Chinese Center of Systematic Medical Malacology. Using RAPD, RFLP and single copy cDNA sequencing we will uncover inter- and infraspecific genetic diversity and/or cryptic species. These techniques have already revealed unique Chinese strains among the S. japonicum complex and Paragonimus spp., and will help us to examine the impact of a major Yangtze civil engineering project, the Three Gorges Dam, on helminth/vector emergence. Ultimately, the extent of genetic diversity will have a bearing on the development of molecular vaccine candidates that cover widely divergent Chinese strains.